Apparatus and method for determining a parameter indicative of the progress of an extracorporeal blood treatment

ABSTRACT

An apparatus and process for extracorporeal treatment of blood ( 1 ) comprising a treatment unit ( 2 ), a blood withdrawal line ( 6 ), a blood return line ( 7 ), a preparation line ( 19 ) and a spent dialysate line ( 13 ). A control unit ( 10 ) is configured to calculate values of a parameter relating to treatment effectiveness based on measures of lactate or citrate or acetate concentration in the spent dialysate line ( 13 ).

PRIORITY CLAIM

The present application is a National Phase of International ApplicationNo. PCT/EP2017/059062, filed Apr. 14, 2017, which claims priority toEuropean Patent Application No. 16166990.8, filed Apr. 26, 2016, theentire contents of each of which are incorporated herein by referenceand relied upon.

The invention relates to an apparatus and to a method for determining aparameter indicative of the progress of an extracorporeal bloodtreatment, in particular a purification treatment whose purpose is toalleviate renal insufficiency, such as hemodialysis orhemodiafiltration.

In a hemodialysis treatment a patient's blood and a treatment liquidapproximately isotonic with blood are circulated in a respectivecompartment of hemodialyzer, so that, impurities and undesiredsubstances present in the blood (urea, creatinine, etc.) may migrate bydiffusive transfer from the blood into the treatment liquid. The ionconcentration of the treatment liquid is chosen such as to correct theions concentration of the patient's blood.

In a treatment by hemodiafiltration, a convective transfer byultrafiltration, resulting from a positive pressure difference createdbetween the blood side and the treatment-liquid side of the membrane, isadded to the diffusive transfer obtained by dialysis.

It is of interest to be able to determine, throughout a treatmentsession, one or more parameters indicative of the progress of thetreatment so as to be able, where appropriate, to modify the treatmentconditions that were initially fixed or to at least inform the patientand the medical personnel about the effectiveness of the treatment.

The knowledge of one or more of the following parameters may make itpossible to follow the progress of the treatment, and for instance mayallow to assess the suitability of the initially fixed treatmentconditions:

-   -   the actual dialysance D or the actual clearance K of the        exchanger for a given solute (the dialysance D and the clearance        K representing the purification performance of the exchanger),    -   the dialysis dose administered after a treatment time t, which,        according to the work of Sargent and Gotch, may be linked to the        dimensionless ratio KT/V, where K is the actual clearance in the        case of urea, T the elapsed treatment time and V the volume of        distribution of urea, i.e. the total volume of water in the        patient (Gotch F. A. and Sargent S. A., “A mechanistic analysis        of the National Cooperative Dialysis Study (NCDS)”, Kidney Int.        1985, Vol. 28, pp. 526-34).

The determination of these parameters requires precise knowledge of aphysical or chemical characteristic of the blood. As it can beunderstood, determination of this characteristic cannot in practice beobtained by direct measurement on a specimen for therapeutic,prophylactic and financial reasons. Indeed, it is out of the questiontaking multiple specimens necessary to monitor the effectiveness of thetreatment from a patient who is often anemic; furthermore, given therisks associated with handling specimens of blood which may possibly becontaminated, the general tendency is to avoid such handling operations;finally, laboratory analysis of a specimen of blood is both expensiveand relatively lengthy, this being incompatible with the desiredobjective of knowing the effectiveness of a treatment while thetreatment is still ongoing. Several methods have been proposed for invivo determining hemodialysis parameters without having to takemeasurements on blood samples.

Document EP 0547025 describes a method for determining the concentrationof a substance, such as sodium, in a patient's blood subjected to ahemodialysis treatment. This method also makes it possible to determinethe dialysance D—for example for sodium—of the hemodialyzer used. Themethod comprises the steps of circulating a first and a secondhemodialysis liquids having different sodium concentrations insuccession through the hemodialyzer, measuring the conductivity of thefirst and second dialysis liquids upstream and downstream of thehemodialyzer, and computing the concentration of sodium in the patient'sblood (or the dialysance D of the hemodialyzer for sodium) from thevalues of the conductivity of the liquid which are measured in the firstand second dialysis liquids upstream and downstream of the hemodialyzer.Document EP 0658352 describes another method for the in vivodetermination of hemodialysis parameters, which comprises the steps of:making at least a first and a second treatment liquids, having acharacteristic (the conductivity, for example) associated with at leastone of the parameters (the ion concentration of the blood, thedialysance D, the clearance K, KT/V, for example) indicative of thetreatment, flow in succession through the hemodialyzer, the value of thecharacteristic in the first liquid upstream of the exchanger beingdifferent from the value of the characteristic in the second liquidupstream of the exchanger; measuring, in each of the first and secondtreatment liquids, two values of the characteristic, respectivelyupstream and downstream of the exchanger; making a third treatmentliquid flow through the exchanger while the characteristic of the secondliquid has not reached a stable value downstream of the exchanger, thevalue of the characteristic in the third liquid upstream of theexchanger being different from the value of the characteristic in thesecond liquid upstream of the exchanger; measuring two values of thecharacteristic in the third liquid, respectively upstream and downstreamof the exchanger; and computing at least one value of at least oneparameter indicative of the progress of the treatment from the measuredvalues of the characteristic in the first, second and third treatmentliquids. Another method for the in vivo determination of thehemodialysis parameters which does not require taking measurements onblood samples is described in document EP 0920877. This method includesthe steps of: making a treatment liquid flow through the exchanger, thistreatment liquid having a characteristic which has an approximatelyconstant nominal value upstream of the exchanger; varying the value ofthe characteristic upstream of the exchanger and then re-establishingthe characteristic to its nominal value upstream of the exchanger;measuring and storing in memory a plurality of values adopted by thecharacteristic of the treatment liquid downstream of the exchanger inresponse to the variation in the value of this characteristic causedupstream of the exchanger; determining the area of a downstreamperturbation region bounded by a baseline and a curve representative ofthe variation with respect to time of the characteristic; and computingthe parameter indicative of the effectiveness of a treatment from thearea of the downstream perturbation region and from the area of anupstream perturbation region bounded by a baseline and a curverepresentative of the variation with respect to time of thecharacteristic upstream of the exchanger.

The above described methods require a relatively short—compared totreatment time—modification of the value of a characteristic of thedialysis liquid (the conductivity, for example) and then there-establishment of this characteristic to its initial value, which isgenerally the prescribed value. Since, deviations from the prescriptionare not desirable and since the above described methods require aminimum duration of the introduced modification, it derives that allthese methods can be carried out only few times during a treatment.

With the aim of further improving the above methods, document US2001004523 describes a solution for continuously determining a parameter(D, Cbin, K, KT/V) indicative of the effectiveness of an extracorporealblood treatment comprising the steps of: causing a succession ofsinusoidal variations in the characteristic (Cd) a treatment liquidupstream of the exchanger, continuously storing in memory a plurality ofvalues (Cd_(in1) . . . Cd_(in) . . . Cd_(inp)) of the characteristic(Cd) upstream of the exchanger, measuring and continuously storing inmemory a plurality of values (Cd_(out1), . . . Cd_(outj) . . .Cd_(outp)) adopted by the characteristic (Cd) downstream of theexchanger in response to the variations in the characteristic (Cd) whichare caused upstream of the exchanger, computing—each time that apredetermined number of new values (Cd_(outj)) of the characteristic(Cd) downstream of the exchanger has been stored—a parameter (D, Cbin,K, KT/V) indicative of the effectiveness of the extracorporeal bloodtreatment, from a first series of values (Cd_(inj)) of thecharacteristic (Cd) upstream of the exchanger, from a second series ofvalues (Cd_(outj)) of the characteristic (Cd) downstream of theexchanger, based on a mathematical model of the influence of thecharacteristic (Cd) on the effectiveness of the treatment.

Finally, EP2687248 describes an apparatus configured to calculate valuesof a parameter relating to treatment effectiveness based on measures ofthe conductivity in the spent dialysate line subsequent to analternating conductivity perturbation continuously imposed on thepreparation line of fresh dialysis fluid.

The advantage of a alternated perturbations in the characteristic of theliquid upstream the dialyzer is that the patient may not be exposed to atreatment liquid very different from the prescribed treatment liquid(for example, one which is too rich or too depleted in sodium).

Although the above methods resulted in certain improvements over thestate of the art, the known solutions still need to perturb thecomposition of the dialysis liquid.

Furthermore, the characteristic in the liquid downstream the dialyzermay be difficult to accurately be measured. Moreover, the hydraulicdelay, the damping effect caused by the dialyzer, and the noiseintroduced by the machine and its components may require toappropriately elaborate the signals detected by the sensors.

It is therefore an object of the present invention to provide anapparatus and a method to reliably calculate an effectiveness parameterduring treatment without impairing on the treatment prescription.

Moreover, it is an auxiliary object providing a method and an apparatuswhich are not very sensitive to incidents or noise or accidentaldetection errors.

Additionally, it is an object providing a method and an apparatus whichmay be implemented with no need of high computational power and withoutcomplex mathematical models.

Another auxiliary object is an apparatus capable of operating in a safemanner.

A further auxiliary object is an apparatus capable of automaticallycalculate the parameter and inform the operator accordingly.

SUMMARY

At least one of the above objects is substantially reached by anapparatus according to one or more of the appended claims.

Apparatus and processes according to aspects of the invention andcapable of achieving one or more of the above objects are here belowdescribed.

A 1^(st) aspect concerns an apparatus for extracorporeal treatment ofblood comprising: a preparation line (19) having one end configured forbeing connected to an inlet of a secondary chamber (4) of a treatmentunit (2), a semi-permeable membrane (5) separating said secondarychamber (4) from a primary chamber of the same treatment unit (2); aspent dialysate line (13) having one end configured for being connectedto an outlet of said secondary chamber (4); a control unit (10)configured for commanding execution of the following steps:

causing a fresh treatment liquid to flow in the preparation line (19)towards the secondary chamber (4) at a flow rate (Qd_(in)), thetreatment liquid including lactate or citrate or acetate;

causing a used treatment liquid to flow in the spent dialysate line (13)at a flow rate (Qd_(out));

receiving one or more measured values of a parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) in the usedtreatment liquid flowing in the spent dialysate line (13);

computing at least one value of a parameter (D, KT) indicative of theeffectiveness of the extracorporeal blood treatment based on:

said one or more measured values of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) of the usedtreatment liquid;

at least one of: said flow rate (Qd_(in)) of fresh treatment liquid andsaid flow rate (Qd_(out)) of used treatment liquid.

In a 2^(nd) aspect according to the 1^(st) aspect, the control unit isfurther configured for receiving one or more values of a parameterrelated to the concentration of lactate or citrate or acetate (Cd_(in))of the fresh treatment liquid flowing in the preparation line (19). Thisstep of receiving may include measuring one or more actual values, orretrieving from a memory one or more preset values, or receiving from auser interface one or more input values of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(in)) of the freshtreatment liquid flowing in the preparation line (19).

In a 3^(rd) aspect according to the 2^(nd) aspect computing at least onevalue of a parameter (D, KT) indicative of the effectiveness of theextracorporeal blood treatment is based on:

said one or more measured values of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) of the usedtreatment liquid;

said one or more values of the parameter related to the concentration oflactate or citrate or acetate (Cd_(in)) of the fresh treatment liquid;

at least one of: said flow rate (Qd_(in)) of fresh treatment liquid andsaid flow rate (Qd_(out)) of used treatment liquid.

In a 4^(th) aspect according to any one of the preceding aspects, thestep of causing a fresh treatment liquid to flow in the preparation line(19) comprises the sub-step of maintaining, at least for a time interval(ΔT), the concentration of the lactate or citrate or acetate (Cd_(in))in the fresh treatment liquid constant at a set value (Cd_(set)) whichrepresents the value of the parameter related to the concentration oflactate or citrate or acetate (Cd_(in)) of the fresh treatment liquidused for computing the at least one value of a parameter (D, KT)indicative of the effectiveness of the extracorporeal blood treatment.

In a 5th aspect according to the preceding aspect said one or moremeasured values of the parameter related to the concentration of lactateor citrate or acetate (Cd_(out)) in the used treatment liquid arerepresentative of measures of the parameter related to the concentrationof lactate or citrate or acetate (Cd_(out)) taken either during saidtime interval (ΔT).

In a 6^(th) aspect according to the 4^(th) aspect said one or moremeasured values of the parameter related to the concentration of lactateor citrate or acetate (Cd_(cut)) in the used treatment liquid arerepresentative of measures of the parameter related to the concentrationof lactate or citrate or acetate (Cd_(out)) taken during a further timeinterval (ΔT′), optionally having same duration of said time interval,delayed by an hydraulic delay with respect to said time interval. Thehydraulic delay is the time required by a unitary mass of fluid to movefrom a predetermined section in the fluid preparation line to thesection in the fluid spent line where measures are taken.

In a 7^(th) aspect according to any one of the preceding aspects, thecontrol unit (10) is further configured for:

receiving a total treatment time (Tt), which is a time during which theapparatus operates with blood in the extracorporeal circuit and apatient connected to the extracorporeal circuit,

maintaining the concentration of the lactate or citrate or acetate inthe fresh treatment liquid constant at said set value (Cd_(set)) duringa time interval (ΔT) lasting for a significant portion of the treatmenttime (Tt) and

calculating a plurality of consecutive times during said time interval(ΔT) the value of the parameter (D, KT) indicative of the effectivenessof the extracorporeal blood treatment.

In a 8^(th) aspect according to the preceding aspect, said significantportion of the treatment time comprises one in the group of:

-   -   at least 10% of said total treatment time (Tt),    -   at least 30% of said total treatment time (Tt),    -   at least 70% of said total treatment time (Tt),    -   the entire treatment total time (Tt).

In a 9^(th) aspect according to any one of the preceding aspects, theapparatus comprises an outlet lactate or citrate or acetateconcentration sensor (50) connected to the control unit (10); whereinthe outlet lactate or citrate or acetate concentration sensor (50) isconfigured for measuring one or more real values of the concentrationtaken by lactate or citrate or acetate in the fluid exiting from thesecondary chamber (4) and wherein the control unit (10) is configured toreceive, as measured value or values of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) in the usedtreatment liquid, the one or more measured real values of the lactate orcitrate or acetate concentration detected by the lactate or citrate oracetate concentration sensor (50).

In a 10^(th) aspect according to the preceding aspect, the outletlactate or citrate or acetate concentration sensor is operative at saidspent dialysate line (13) or on a line connected to the spent dialysateline (13) or to the outlet of said secondary chamber (4).

In an 11^(th) aspect according to any one of the preceding aspects, theapparatus includes at least a blood pump configured to operate on anextracorporeal blood circuit connectable to the primary chamber of saidblood treatment unit, said control unit being connected to the bloodpump and being configured to:

operate the blood pump to cause flow of a patient's blood in theextracorporeal blood circuit at a blood flow rate (Qb),

receive or store a value representative of the concentration of lactatein blood or in a blood component (Cb_(in)).

In a 12^(th) aspect according to any one of the preceding aspects, theparameter (D, KT) indicative of the effectiveness of the extracorporealblood treatment is calculated based on:

at least one measured value of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) in the usedtreatment liquid;

at least one measured value of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(in)) of the freshtreatment liquid;

said flow rate (Qd_(in)) of fresh treatment liquid;

said value representative of the concentration of lactate or or citrateor acetate in blood or in a blood component (Cb_(in)).

In a 13^(th) aspect according to any one of the preceding aspects fromthe 5^(th) to the 12^(th), the control unit—at least during said timeinterval (ΔT) or during said further time interval (ΔT′)—is configuredto keep constant the flow rate (Qd_(in)) of fresh treatment liquid inthe preparation line (19), the flow rate (Qb) of patient's blood in theextracorporeal blood circuit, the flow rate (Q_(F)) of ultrafiltrationflow through the semipermeable membrane (for instance theultrafiltration flow rate may be kept at zero).

In a 14^(th) aspect according to any one of the preceding aspects theparameter indicative of the effectiveness of the extracorporeal bloodtreatment is lactate or citrate or acetate dialysance (D).

In a 15^(th) aspect according to the preceding aspect lactate or citrateor acetate dialysance (D) is calculated using the following formula:D=(Qdin×(Cdin Cdout)+QF×Cdout)/(Cdin Cbin)

where

D is the calculated value of dialysance for lactate or citrate oracetate,

Cd_(out) is the measured value of the parameter related to theconcentration of lactate or citrate or acetate, in particular thelactate or citrate or acetate concentration, of the used treatmentliquid;

Cd_(in) is measured value of the parameter related to the concentrationof lactate or citrate or acetate, in particular the lactate or citrateor acetate concentration, of the fresh treatment liquid;

Qd_(in) is the flow rate of fresh treatment liquid;

Cb_(in) is the value representative of the concentration of lactate orcitrate or acetate in blood or in a blood component;

Q_(F) is the value of ultrafiltration flow rate through thesemipermeable membrane.

In a 16^(th) aspect according to the preceding aspect, lactate orcitrate or acetate dialysance—when no ultrafiltration through thesemipermeable membrane is present (Q_(F)=0)—is calculated as follows:D=D0=(Qdin ×(Cdin Cdout))/(Cdin Cbin)

In a 17^(th) aspect according to any one of the preceding aspects, thecontrol unit is configured for causing the fresh treatment liquid toflow in the preparation line (19) towards the secondary chamber (4) at aconstant lactate concentration (Cd_(in)), which is set at a set value(Cd_(set)) comprised between 35 mmol/l and 45 mmol/l.

In a 18^(th) aspect according to any one of the preceding aspects, thecontrol unit is configured for causing the fresh treatment liquid toflow in the preparation line (19) towards the secondary chamber (4) at aconstant lactate concentration (Cd_(in)), which is set at a set value(Cd_(set)) comprised between 38 mmol/1 and 42 mmol/l.

In a 19^(th) aspect according to any one of the preceding aspects, thevalue (Cb_(in)) representative of the concentration of lactate in bloodor in a blood component is a known value selected in the range comprisedbetween 1 and 5 mmol/l.

In a 20^(th) aspect according to any one of the preceding aspects, theone or more measured values of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) of the usedtreatment liquid are taken after 30 minutes from start of theextracorporeal blood treatment.

In a 21^(th) aspect according to any one of the preceding aspects, theparameter indicative of the effectiveness of the extracorporeal bloodtreatment is lactate dialysance (D), and the control unit is configuredto calculate the dialysance for a given solute different from lactatefrom:

the calculated value of the lactate dialysance,

one or more established relationships between the value of mass transfercoefficient (K0.A)_(lactate) for lactate to the value of mass transfercoefficient (K0.A)_(solute) for the given solute, the mass transfercoefficient reflecting a solute diffusion through the membrane.

In a 22^(nd) aspect according to any one of the preceding aspects, theparameter indicative of the effectiveness of the extracorporeal bloodtreatment is lactate dialysance (D), and the control unit is configuredto calculate dialysance for a given solute different from lactate asfollows:

deriving (302) a mass transfer coefficient for lactate (K0.A)_(lactate)of the membrane of the treatment unit from the calculated value of thedialysance for lactate;

determining (303) a mass transfer coefficient (K0.A)_(solute) of themembrane of the treatment unit for the given solute based on the valueof the mass transfer coefficient (K0.A)_(lactate) for lactate;

calculating (304) the dialysance for the given solute based on the masstransfer coefficient (K0.A)_(solute) for the given solute.

In a 23^(rd) aspect according to any one of the preceding two aspects,the lactate dialysance and the dialysance for a given solute differentfrom lactate are calculated at same values of:

the flow rate (Qd_(in)) of fresh treatment liquid,

the ultrafiltration flow rate (Q_(F)) through the semipermeablemembrane;

and making reference to a same blood flow rate (Qb) in theextracorporeal circuit.

In a 24^(th) aspect according to any one of the preceding three aspects,the control unit is configured for:

identifying the solute for which dialysance is to be calculated,

determining if a mass transfer time of the solute through red bloodcells is greater, optionally at least 5 times greater, than a blooddwell time of blood flowing through the blood treatment unit,

using the value of the plasma flow rate at the inlet of the bloodtreatment unit (Qp_(in)) as effective value of the blood flow rate forthe purpose of calculating the solute mass transfer coefficient(K0.A)_(lactate), if it has been determined that the mass transfer timeof the solute through red blood cells is grater, optionally 5 timesgreater, than blood dwell time in blood treatment unit, whereQp_(in)=(1-Hct) Qb_(in),

with Hct being the hematocrit of blood in the arterial line at the inletof the blood treatment unit and (Qb_(in)) the blood flow rate at theinlet of the blood treatment unit.

In a 25^(th) aspect according to any one of the preceding four aspects,the mass transfer coefficient for lactate (K0.A)_(lactate) of themembrane of the treatment unit is derived by:

measuring or calculating (301) the value of dialysance for lactate, inparticular at zero ultrafiltration,

deriving (302) a mass transfer coefficient for lactate (K0.A)_(lactate)of the membrane of the treatment unit from:

the calculated value of the dialysance for lactate, in particular atzero ultrafiltration,

one or more of values of: the flow rate (Qd_(in)) of fresh treatmentliquid, the flow rate (Qd_(out)) of spent dialysate liquid, theultrafiltration flow rate (Q_(F)) through the semipermeable membrane,

the blood flow rate (Qb) or the plasma flow rate (Qp), in particular oneof the plasma flow rate at the inlet of the blood treatment unit(Qp_(in)) and the blood flow rate at the inlet of the blood treatmentunit (Qb_(in)).

In a 26^(th) aspect according to any one of the preceding five aspects,the mass transfer coefficient for lactate (K0.A)_(lactate) of themembrane of the treatment unit is derived by:

measuring or calculating (301) the value of dialysance for lactate, atzero ultrafiltration,

deriving (302) a mass transfer coefficient for lactate (K0.A)_(lactate)of the membrane of the treatment unit from:

the calculated value of the dialysance for lactate, at zeroultrafiltration,

one or more of values of: the flow rate (Qd_(in)) of fresh treatmentliquid, the flow rate (Qd_(out)) of spent dialysate liquid, theultrafiltration flow rate (Q_(F)) through the semipermeable membrane,

the blood flow rate (Qb) or the plasma flow rate (Qp), in particular oneof the plasma flow rate at the inlet of the blood treatment unit

(Qp_(in)) and the blood flow rate at the inlet of the blood treatmentunit (Qb_(in)).

In a 27^(th) aspect according to any one of the preceding six aspects,the mass transfer coefficient (K0.A)_(solute) for the given solute isderived (303) using one or more established relationships, optionallyone or more known ratios, between the value of the mass transfercoefficient (K0.A)_(lactate) for lactate to the value of the masstransfer coefficient (K0.A)_(solute) for the given solute.

In a 28^(th) aspect according to any one of the preceding aspect,calculating dialysance of the given solute (304) comprises calculatingsaid dialysance for the given solute based on:

one or more of values of: the flow rate (Qd_(in)) of fresh treatmentliquid, the flow rate (Qd_(out)) of spent dialysate liquid, theultrafiltration flow rate (Q_(F)) through the semipermeable membrane,

the blood flow rate (Qb) or the plasma flow rate (Qp), in particular oneof the plasma flow rate at the inlet of the blood treatment unit(Qp_(in)) and the blood flow rate at the inlet of the blood treatmentunit (Qb_(in)),

the determined mass transfer coefficient for the given solute(K0.A)_(solute).

In a 29^(th) aspect according to any one of the preceding four aspects,the step of deriving a mass transfer coefficient for lactate(K0.A)_(lactate) of the membrane of the treatment unit comprises:

measuring or calculating (301) the value of dialysance for lactate atzero ultrafiltration, and

calculating (302) the mass transfer coefficient for lactate(K0.A)_(lactate) of the membrane of the treatment unit using thecalculated value of the dialysance for lactate at zero ultrafiltration.

In a 30^(th) aspect according to any one of the preceding two aspects,the step of calculating dialysance of the given solute (304) comprises:

first determining the value of the dialysance for the given solute, atzero ultrafiltration, based upon:

the determined mass transfer coefficient for the given solute(K0.A)_(solute);

one of: the flow rate (Qd_(in)) of fresh treatment liquid, the flow rate(Qd_(out)) of spent dialysate liquid;

the blood flow rate (Qb) or the plasma flow rate (Qp), in particular oneof the plasma flow rate at the inlet of the blood treatment unit(Qp_(in)) and the blood flow rate at the inlet of the blood treatmentunit (Qb_(in));

then determining dialysance for the given solute at non zeroultrafiltration based on:

the determined value of the dialysance for the given solute at zeroultrafiltration, and the value of the ultrafiltration flow rate; or

the determined value of the dialysance for the given solute at zeroultrafiltration, the value of the ultrafiltration flow rate (Q_(F))through the semipermeable membrane, and the blood flow rate (Qb) orplasma flow rate (Qp), in particular one of the plasma flow rate at theinlet of the blood treatment unit (Qp_(in)) and the blood flow rate atthe inlet of the blood treatment unit (Qb_(in)).

In a 31^(st) aspect according to any one of the preceding aspects, theparameter indicative of the effectiveness of the extracorporeal bloodtreatment based comprises lactate dialysis dose (KT)_(lactate) deliveredover a reference time period (T).

In a 32^(nd) aspect according to the preceding aspect, the control unit(10) is configured to calculate lactate dialysis dose (KT)_(lactate) by:

determining the total effluent volume flown in the spent dialysate line(EV) in the course of the reference time period (T), measuring thelactate concentration of said total effluent volume,

calculating (KT) based on the lactate concentration in blood, lactateconcentration in the fresh treatment liquid and lactate concentration insaid effluent volume, optionally using the following formula:(KT)_(lactate) =EV*((Cd _(in) −Cd _(out))/(Cd _(in) −Cb _(in)))

where

EV: effluent volume,

Cd_(out) is the lactate concentration of the used treatment liquid;

Cd_(in) is the lactate concentration of the fresh treatment liquid;

Cb_(in) is the concentration of lactate in blood or in a blood component(plasma);

In a 33^(rd) aspect according to the 31^(st) aspect, the control unit(10) is configured to calculate lactate dialysis dose (KT)_(lactate) by:receiving said one or more values of a parameter related to theconcentration of lactate (Cd_(in)) of the fresh treatment liquid flowingin the preparation line (19) measured during the reference time period(T),

receiving values of the following flow rates, which remain constantduring the time period (T): blood flow rate (Qb), fresh treatment liquidflow rate (Qd_(in)) or used treatment liquid flow rate (Qd_(out)), and,if present, ultrafiltration flow rate (Q_(F)),

calculating a value of lactate dialysance (D_(lactate)) for said timeperiod (T),

calculating a lactate dialysis dose (KT)_(lactate) for said time period(T) multiplying the duration of the time period (T) times the lactatedialysance (D_(lactate)) determined for the same time period (T).

In a 34^(th) aspect according to any one of the preceding aspects, totaltreatment time (Tt) comprises a plurality of consecutive reference timeperiods (Ti), each reference time period (Ti) being a fraction of thetotal treatment time, further wherein blood flow rate (Qb), freshtreatment liquid flow rate (Qd_(in)), used treatment liquid flow rate(Qd_(out)) and, if present, ultrafiltration flow rate (Q_(F)) remainconstant at respective values during each respective of said consecutivereference time periods (Ti).

In a 35^(th) aspect according to the preceding aspect, the totaldialysis dose for lactate (KTt)_(lactate) is calculated as follows:

calculating for each of said time period a respective partial dialysisdose for lactate (KT)i_(lactate),

calculating the total dialysis dose for lactate (KTt)_(lactate) makingthe sum of each partial dialysis dose for lactate (KT)i_(lactate) foreach reference time period Ti as follows: (KTt)_(lactate)=Σ(KT)i_(lactate)

In a 36^(th) aspect according to the preceding aspect the total dialysisdose for lactate (KTt)_(lactate) is calculated as follows:

calculating for each of said time period a respective partial dialysisdose for lactate (KT)i_(lactate) using formula:(KT)i _(lactate) =EVi*((Cd _(in) −Cd _(out))/(Cd _(in) −Cb _(in)))

where

EVi: effluent volume collected during each respective time interval(Ti),

Cd_(out) is the lactate concentration of the used treatment liquidduring each respective time interval (Ti),

Cd_(in) is the lactate concentration of the fresh treatment liquidduring each respective time interval (Ti),

Cb_(in) is the concentration of lactate in blood or in a blood component(plasma) during each respective time interval (Ti).

calculating the total dialysis dose for lactate (KTt)_(lactate) makingthe sum of each partial dialysis dose for lactate (KT)i_(lactate) foreach reference time period Ti as follows:(KTt)_(Lactate)=Σ(K T)i _(lactate)

In a 37^(th) aspect according to the 35^(th) aspect the control unit isconfigured to:

receiving said one or more values of a parameter related to theconcentration of lactate (Cd_(in)) of the fresh treatment liquid flowingin the preparation line (19) measured during each reference time period(Ti),

receiving values of the following flow rates, which remain constantduring each time period (Ti): blood flow rate (Qb), fresh treatmentliquid flow rate (Qd_(in)) or used treatment liquid flow rate(Qd_(out)), and, if present, ultrafiltration flow rate (Q_(F)),

calculating a value of lactate dialysance (Di_(lactate)) for each timeperiod (Ti),

calculating a lactate dialysis dose (KT)i_(lactate) for each one of saidtime periods (Ti) multiplying the duration of each further time period(Ti) times the respective lactate dialysance (Di_(lactate)) determinedfor the same further time period (Ti);

summing the calculated lactate doses each of said time periods (Ti) toobtain the total lactate dose for the reference period: Σ(KT)i_(lactate)=Σ(Di_(lactate)·Ti)

In a 38^(th) aspect according to the preceding aspect, calculating (206)the value of the lactate dialysance (Di_(lactate)) for each time period(Ti) is made as follows:

calculating the value of dialysance (Di_(lactate)) at prescribedconstant values of blood flow rate (Qb), fresh treatment liquid flowrate (Qd_(in)) or used treatment liquid flow rate (Qd_(out)) and, ifpresent, ultrafiltration flow rate (Q_(F));

calculating the mass transfer coefficient for lactate (K0.A)_(Lactate);

based on the (K0.A)_(lactate) and on respective constant values of bloodflow rate (Qb), fresh treatment liquid flow rate (Qdi_(n)) or usedtreatment liquid flow rate (Qd_(out)) and, if present, ultrafiltrationflow rate (QF) at each subsequent time period (Ti), calculatingdialysance (Di)_(lactate) for each subsequent of said time periods (Ti).

In a 39^(th) aspect according to any one of the preceding aspects, thecontrol unit (10) is configured to automatically trigger a newcomputation of the at least one value of said parameter (D, KT)indicative of the effectiveness of the extracorporeal blood treatmentevery time the control unit receives an indication that there has been achange or detects a change in one or more of following flow rates: bloodflow rate (Qb), fresh treatment liquid flow rate (Qdi_(n)), usedtreatment liquid flow rate (Qd_(out)) and, if present, ultrafiltrationflow rate (Q_(F)).

In a 40^(th) aspect according to any one of the preceding aspects, thecontrol unit (10) is configured to execute one or both of:

determine presence of recirculation at fistula level (step 204),

calculate an amount of recirculation at fistula level (step 204), bycomparing the computed value of the parameter (D, KT) indicative of theeffectiveness of the extracorporeal blood treatment with a referencevalue for the same parameter.

In a 41^(st) aspect according to the preceding aspect, wherein thereference value is a constant dialysance reference value or a referencevalue which is a lactate or citrate or acetate dialysance or a lactateor citrate or acetate dialysis dose for a same patient in a previoustreatment.

In a 42^(nd) aspect according to any one of the preceding aspects, theapparatus comprises said treatment unit (2), wherein:

-   -   the preparation line (19) has one end connected to an inlet of        the secondary chamber (4) of the treatment unit (2),    -   the spent dialysate line (13) has one end connected to the        outlet of said secondary chamber (4),    -   a blood withdrawal line (6) is connected at an inlet of the        primary chamber (3) and    -   a blood return line (7) is connected at an outlet of the primary        chamber (3).

A 43^(rd) aspect concerns a method of controlling an apparatus forextracorporeal treatment of blood, the apparatus being of the typedisclosed in any one of the preceding claims.

A 44^(th) aspect concerns a method of controlling an apparatus forextracorporeal treatment of blood, the apparatus being of the typecomprising:

a preparation line (19) having one end configured for being connected toan inlet of a secondary chamber (4) of a treatment unit having a primarychamber (3) and said secondary chamber (4) separated by a semi-permeablemembrane;

a spent dialysate line (13) having one end configured for beingconnected to an outlet of said secondary chamber (4);

a blood withdrawal line (6) connected at an inlet of the primary chamber(3); and

a blood return line (7) connected at an outlet of the primary chamber(3).

In a 45^(th) aspect according to any one of the preceding two aspects,the method comprises execution of the following steps:

causing a patient's blood to flow in the blood withdrawal line, in theprimary chamber and in the blood return line,

causing a fresh treatment liquid to flow in the preparation line (19)towards the secondary chamber (4) at a flow rate (Qd_(in)), thetreatment liquid including lactate or citrate or acetate;

causing a used treatment liquid to flow in the spent dialysate line (13)at a flow rate (Qd_(out));

receiving one or more measured values of a parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) in the usedtreatment liquid flowing in the spent dialysate line (13);

computing at least one value of a parameter (D, KT) indicative of theeffectiveness of the extracorporeal blood treatment based on:

said one or more measured values of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) of the usedtreatment liquid;

at least one of: said flow rate (Qd_(in)) of fresh treatment liquid andsaid flow rate (Qd_(out)) of used treatment liquid.

In a 46^(th) aspect according to the preceding aspect, the methodcomprises

receiving one or more values of a parameter related to the concentrationof lactate or citrate or acetate (Cd_(in)) of the fresh treatment liquidflowing in the preparation line (19);

computing at least one value of a parameter (D, KT) indicative of theeffectiveness of the extracorporeal blood treatment based on:

said one or more measured values of the parameter related to theconcentration of lactate or citrate or acetate (Cd_(out)) of the usedtreatment liquid;

said one or more values of the parameter related to the concentration oflactate or citrate or acetate (Cd_(in)) of the fresh treatment liquid;

at least one of: said flow rate (Qd_(in)) of fresh treatment liquid andsaid flow rate (Qd_(out)) of used treatment liquid.

In a 47^(th) aspect according to any one of the preceding four aspects,the method comprises executing the steps the control unit of aspectsfrom the 1^(st) to the 42^(nd) is configured to execute.

A 48^(th) aspect concerns a data carrier including instructionsexecutable by a control unit of a blood treatment apparatus, inparticular the blood treatment apparatus of any one of claims of aspectsfrom the 1^(st) to the 42^(nd), wherein the instructions are configuredsuch that, when executed by the control unit, they cause execution ofthe method according to any one of aspects from the 43^(rd) to the47^(th).

In a 49^(th) aspect according to the preceding aspect, the data carrieris a RAM, a ROM, an EPROM, an optical or a magnetic disc, anelectromagnetic wave, a mass memory storage device such as an Hard Diskor a flash memory bank.

Finally according to a 50^(th) aspect, it is a currently preferredoption to use a dialysis liquid containing lactate and to measure spentand optionally fresh dialysate lactate concentration for thedetermination of the effectiveness parameter. Alternatively, othersuitable substances that have similar properties as lactate are citrateand acetate. It is however to be noted that their concentrations in thefresh treatment liquid (e.g. in the fresh dialysis fluids) are muchsmaller than lactate, (0 to 5 mmol/l for acetate and 0 to 2 mmol/l forcitrate): therefore the concentration gradients for acetate or citratebetween the dialysis liquid and patient blood is much smaller than forlactate, with the result that the measure of concentration of acetate orof citrate in the spent dialysate line may be more difficult and lessaccurate.

DESCRIPTION OF THE DRAWINGS

Aspects of the invention are shown in the attached drawings, which areprovided by way of non-limiting example, wherein:

FIG. 1 shows a concentration vs. time diagram showing the profile of theconcentration of lactate in the fresh dialysate line, according to anaspect of the invention;

FIG. 2 shows a concentration vs. time diagram showing the profile of theconcentration of lactate in the spent dialysate line, according toanother aspect of the invention;

FIG. 3 shows a schematic diagram of a blood treatment apparatusaccording to one aspect of the invention;

FIG. 4 shows a schematic diagram of an alternative embodiment of a bloodtreatment apparatus according to another aspect of the invention; and

FIG. 5 is a schematic flowchart of a method according to one aspect ofthe invention.

FIG. 6 is a schematic flowchart of a further method according to oneaspect of the invention

DETAILED DESCRIPTION

Non-limiting embodiments of an apparatus 1 for extracorporeal treatmentof blood—which may implement innovative aspects of the invention—areshown in FIGS. 3 and 4. The apparatus 1 may be configured to determine aparameter indicative of the effectiveness of the treatment delivered toa patient (here below also referred to as ‘effectiveness parameter’). Inbelow description and in FIGS. 3 and 4 same components are identified bysame reference numerals.

FIG. 3 shows an apparatus 1 configured to deliver any one of treatmentslike hemodialysis and hemodiafiltration, while FIG. 4 shows an apparatusconfigured to deliver hemodialysis or ultrafiltration treatments.

The apparatus 1 comprises a treatment unit 2 (such as a hemofilter, ahemodiafilter, a dialyzer and the like) having a primary chamber 3 and asecondary chamber 4 separated by a semi-permeable membrane 5; dependingupon the treatment, the membrane of the filtration unit may be selectedto have different properties and performances.

A blood withdrawal line 6 is connected to an inlet of the primarychamber 3, and a blood return line 7 is connected to an outlet of theprimary chamber 3. In use, the blood withdrawal line 6 and the bloodreturn line 7 are connected to a needle or to a catheter or other accessdevice (not shown) which is then placed in fluid communication with thepatient vascular system, such that blood may be withdrawn through theblood withdrawal line, flown through the primary chamber and thenreturned to the patient's vascular system through the blood return line.An air separator, such as a bubble trap 8 may be present on the bloodreturn line; moreover, a safety clamp 9 controlled by a control unit 10may be present on the blood return line downstream the bubble trap 8.The control unit may comprise a digital processor (CPU) and a memory (ormemories), an analogical type circuit, or a combination thereof asexplained in greater detail in below section dedicated to the ‘controlunit’. A bubble sensor 8 a, for instance associated to the bubble trap 8or coupled to a portion of the line 7 between bubble trap 8 and clamp 9may be present: if present, the bubble sensor is connected to thecontrol unit 10 and sends to the control unit signals for the controlunit to cause closure of the clamp 9 in case one or more bubbles abovecertain safety thresholds are detected. As shown in FIG. 3, the bloodflow through the blood lines is controlled by a blood pump 11, forinstance a peristaltic blood pump, acting either on the blood withdrawalline (as shown in FIG. 3) or on the blood return line.

An operator may enter a set value for the blood flow rate Qb: thecontrol unit 10, during treatment, is configured to control the bloodpump based on the set blood flow rate. It is noted that the control unit10 may also be connected to a user interface 12, for instance a graphicuser interface, which receives operator's inputs (such as the set valuefor the blood flow rate) and displays the apparatus outputs. Forinstance, the graphic user interface 12 may include a touch screen forboth displaying outputs and allowing user entries, or a display screenand hard keys for entering user's inputs, or a combination thereof.

A spent dialysate line 13 configured for evacuating an effluent fluidcoming from the secondary chamber 4 is connected, at one end, to anoutlet of the secondary chamber 4 and, at its other end, to a wastewhich may be a discharge conduit or an effluent fluid container 14(dashed lines in FIGS. 3 and 4) collecting the fluid extracted from thesecondary chamber. An effluent fluid pump 17 operates on the spentdialysate line under the control of control unit 10 to regulate the flowrate Qd_(0t) of effluent fluid exiting the secondary chamber 4 andflowing through the spent dialysate line. The apparatus may also includean ultrafiltration line 25 branching off the spent dialysate line 13 andprovided with a respective ultrafiltration pump 27 also controlled bycontrol unit 10 to cause a flow rate Q_(F) along the ultrafiltrationline. The embodiment of FIG. 3 presents a pre-dilution fluid line 15connected to the blood withdrawal line: this line 15 suppliesreplacement fluid from an infusion fluid container 16 connected at oneend of the pre-dilution fluid line. Although FIG. 3 shows a container 16as source of infusion fluid, this should not be interpreted in alimitative manner: indeed, the infusion fluid may also come from an online preparation section 100 part of the apparatus 1. Note thatalternatively to the pre-dilution fluid line the apparatus of FIG. 3 mayinclude a post-dilution fluid line (15′ represented with dashed lines inFIG. 3) connecting an infusion fluid container or the on linepreparation section to the blood return line. Finally, as a furtheralternative, the apparatus of FIG. 3 may include both a pre-dilution anda post infusion fluid line: in this case each infusion fluid line may beconnected to a respective infusion fluid container or the two infusionfluid lines may receive infusion fluid from a same source of infusionfluid such as a same infusion fluid container or the online preparationsection 100. In accordance with a possible variant, it is noted that thesource of infusion fluid may be an online preparation section part ofthe apparatus 1 (i.e. the device 100 described herein below or adistinct device analogous to device 100 and connected to the infusionline or lines) supplying fluid to the post and/or pre dilution lines.Furthermore, an infusion pump 18 operates on the infusion line 15 toregulate the flow rate Q_(INF1) through the infusion line 15. Note thatin case of two infusion lines (pre-dilution and post-dilution) eachinfusion line may be provided with a respective infusion pump toregulate the respective flow rate Q_(INF1), Q_(INF2).

The apparatus of FIG. 3, further includes a fluid preparation line 19connected at one end with a water inlet and at its other end with theinlet of the secondary chamber 4 of the filtration unit for supplyingfresh treatment liquid to the secondary chamber 4. A dialysis fluid pump21 works on the fluid preparation line under the control of said controlunit 10, to supply fluid from a source of fresh treatment liquid (suchas a container or the section 100 for on line preparing fresh dialysisliquid) to the secondary chamber 4 at a flow rate Qd_(in).

In the example of FIGS. 3 and 4, the line 19 links the hemodialyzer orhemodiafilter 2 to a section 100 for preparing the dialysis liquid:section 100 comprises a main line 101, the upstream end of which isdesigned to be connected to a supply of water. A first secondary line102 and a second secondary line 103 are connected to the main line 101and are configured to at least supply the necessary quantity of a bufferand the necessary quantity of electrolytes. The first secondary line102, which may be looped back onto the main line 101, is configured forfitting a first container 104, such as a bag or cartridge or othercontainer, containing a buffer. Line 102 is furthermore equipped with afirst metering pump 105 for dosing the buffer into the fresh treatmentliquid: as shown in FIG. 3 the pump may be located downstream of thefirst container 104. The operation of the pump 105 may be controlled bythe control unit 10 based upon the comparison between: 1) a set pointvalue for the buffer concentration of the solution forming at thejunction of the main line 101 and the first secondary line 102, and 2)the value of the buffer concentration of this mixture measured by afirst probe 106 located either in the first secondary line downstreamthe first container 104 or in the main line 101 immediately downstreamof the junction between the main line 101 and the first secondary line102. Furthermore, the free end of the second secondary line 103 isintended to receive fluid from second container 107 containing aconcentrated saline solution, e.g. electrolytes such as sodium chloride,calcium chloride, magnesium chloride and potassium chloride. In avariant also the second secondary line 103 may be looped back onto themain line. Moreover, it is possible envisaging a plurality ofindependent second secondary lines 103 in the case one wishes to feedseparate electrolytes or electrolyte compositions from respectivecontainers. Note that the second secondary line 103 is equipped with asecond metering pump 108 for dosing electrolytes into the freshtreatment liquid; operation of the second metering pump depends on thecomparison between 1) a conductivity setpoint value or an electrolyteconcentration setpoint value for the solution forming at the junction ofthe main line 101 with the second secondary line 103, and 2) the valueof the conductivity or electrolyte concentration of this solutionmeasured by a second probe 109 located either in the second secondaryline downstream of second container 107 or in the main line 12immediately downstream of the junction between the main line 12 and thesecondary line 103. Note that the specific nature of the concentratescontained in containers 104 and 107 may be varied depending upon thecircumstances and of the type of fresh treatment fluid to be prepared.Moreover, the nature and the position of the first and second probes maydepend upon the type of buffer used, the type of electrolyteconcentrate(s) adopted and upon the specific configuration of thecircuit formed by the main line and the secondary lines. Furthermore, asalready mentioned, more than two secondary lines, with respectiveconcentrate containers and respective metering pumps may be in case aplurality of different type of substances need to be added for thepreparation of the fresh treatment fluid.

In accordance with one aspect of the present invention the buffer is orcomprises lactate. In particular, the first container may host a lactateconcentrate solution: the metering pump(s) and the dialysis pump may becontrolled such as to generate a fresh treatment fluid at a desiredlactate concentration (e.g. at 40 mmol/l of lactate concentration).Within the meaning of the present description and claims, lactateincludes L-lactate, D-lactate, any mixture of D-lactate with L-lactate,or other lactate based compositions. Note that alternatively to the online preparation section 100, the apparatus 1 may use one or morepreformed bags of fresh treatment fluid at the desired concentration forthe buffer (lactate) and for the substances (electrolytes, nutrientsetcetera).

The embodiment of FIG. 4 shows an alternative apparatus 1 designed fordelivering any one of treatments like hemodialysis and ultrafiltration.In the apparatus shown in FIG. 4 the same components described for theembodiment of FIG. 3 are identified by same reference numerals and thusnot described again. In practice, differently from the hemodiafiltrationapparatus of FIG. 3, the apparatus of FIG. 4 does not present anyinfusion line.

In each one of the above described embodiments, flow sensors 110, 111(either of the volumetric or of the mass type) may be used to measureflow rate in each of the lines. Flow sensors are connected to thecontrol unit 10. In the example of FIG. 3 where the infusion line 15 andthe ultrafiltration line 25 lead to a respective container or bag 16,23, scales may be used to detect the amount of fluid delivered orcollected. For instance, the apparatus of figure includes a first scale33 operative for providing weight information W₁ relative to the amountof the fluid collected in the ultrafiltration container 23 and a secondscale 34 operative for providing weight information W₂ relative to theamount of the fluid supplied from infusion container 16. In theembodiment of FIG. 4, the apparatus includes a first scale 33 operativefor providing weight information W₁ relative to the amount of the fluidcollected in the ultrafiltration container 23. The scales are allconnected to the control unit 10 and provide said weight informationW_(i) for the control unit to determine the actual quantity of fluid ineach container as well as the actual flow rate of fluid supplied by orreceived in each container.

In the example of FIGS. 3 and 4, in order to control the fluid balancebetween the quantity of fluid supplied to the secondary chamber 4 andthe quantity of fluid extracted from the secondary chamber, theflow-meters 110, 111 positioned on the fresh dialysate line 19 and onthe spent dialysate line 13 provide the control unit with signalsindicative of the flow of fluid through the respective lines and thescale or scales provide weight information which allow the control unitto derive the flow rate through the ultrafiltration line 25 and, ifpresent, through the infusion line 15. The control unit is configured tocontrol at least pumps 17, 21 and 27 (in case of FIG. 3 also pump 18) tomake sure that a prefixed patient fluid removal is achieved in thecourse of a prescribed treatment time, as required by the prescriptionprovided to the control unit, e.g. via user interface 12. Note thatother fluid balance systems may be used: for instance in case theapparatus includes a container as source of fresh treatment fluid and acontainer to collect waste, then scales may be used to detect the amountof fluid delivered or collected by each container and then inform thecontrol unit accordingly. As a further alternative, systems based onvolumetric control may be used where the preparation line 19 and thespent dialysate line 13 are connected to a balance chamber systemassuring that—at each instant—the quantity of liquid flowing into line19 is identical to the quantity of fluid exiting from line 13.

From a structural point of view one or more, containers 104, 107, 16, 23may be disposable plastic containers. The blood lines 6, 7 lines and thefiltration unit may also be plastic disposable components which may bemounted at the beginning of the treatment session and then disposed ofat the end of the treatment session. Pumps, e.g. peristaltic pumps orpositive displacement pumps, have been described for regulating fluidflow through each of the lines; however, it should be noted that otherflow regulating devices may alternatively be adopted such as for examplevalves or combinations of valves and pumps. The scales may comprisepiezoelectric sensors, or strain gauges, or spring sensors, or any othertype of transducer able to sense forces applied thereon. As alreadyexplained, the conductivity sensors may be replaced by concentrationsensors.

Measure of the Parameter Indicative of Effectiveness of Blood Treatment

The operation of the above apparatus for measuring a parameterindicative of the effectiveness of the blood treatment is now described,with reference to the attached figures and to the flowchart of FIGS. 5and 6.

The control unit 10 is configured to operate the blood pump and causeflow of a patient's blood in the extracorporeal blood circuit at a bloodflow rate Qb: for example the blood flow rate may be set by the useracting on the user interface 12, or it may be pre-stored in a memoryassociated to the control unit or it may be automatically calculated setby the control unit based on certain operative conditions (e.g. keepingpressure upstream the blood pump above a minimum threshold); the controlunit 10 also commands pumps 105, 108 and 21 and is configured forcausing the preparation of a treatment liquid in section 100 and theflow of the freshly prepared treatment liquid in line 19 and into thesecondary chamber 4. The control unit may receive, e.g. via userinterface 12, at least one prescription value Cd_(set) for lactateconcentration Cd_(in) of the treatment liquid which should be keptduring the treatment (step 201) and control the first metering pumpaccordingly. Note that the control unit 10 may also receive set valuesfor the conductivity of the fresh treatment liquid, or for theconcentration of at least one substance (e.g. sodium and/or otherelectrolytes) in the fresh treatment liquid and, based on this value(s),control the second and any further metering pump(s) accordingly.

Note that the prescription value for lactate concentration or for othersubstances may be constant or it may vary according to a prefixedprofile during the treatment. FIG. 1 shows the case of a prescriptionfor lactate which is constant during a first portion of treatment at aset value of 40 mmol/l and then moved to a set value of 35 mmol/l for asecond portion of the treatment. FIG. 2 shows the behavior of lactateconcentration in the spent dialysate line 13 in a case where theprescription for lactate of FIG. 1 is imposed in the fresh treatmentliquid in fluid preparation line 19 The control unit 10 is alsoconfigured for supplying fresh treatment fluid to the secondary chamber4 at flow rate Qd_(in) and for causing a used treatment liquid to exitthe chamber 4 and flow in the spent dialysate line 13 at flow rateQd_(out): in other words the control unit is configured to receive orcalculate the desired value for effluent flow rate Qd_(out) and tocommand the effluent pump 17 accordingly, and to receive or calculatethe desired value of flow rate of fresh treatment liquid Qd_(in) and tocommand pump 21 accordingly. The control unit 10 is also responsible forcontrolling the ultrafiltration pump (if present) and any infusion line18 (if present) in order to cause a flow of effluent fluid through theultrafiltration line and a flow of infusion fluid through the one ormore infusion lines. Note that for instance the control unit 10 may beconfigured to receive set values (e.g. via the user interface 12) for anumber of fluid flow rates (e.g., one or more of Q_(INF1), Q_(INF2),Q_(F), Qd_(in), Qd_(out), Q_(WLR) this latter being representative ofthe weight loss rate), or corresponding volumes for each fluid, andcalculate the set values for the remaining fluid flow rates based ondesired conditions or prescriptions.

For example, referring to FIG. 3, considering that:Q _(F) =Q _(INF1) +Q _(INF2) +Q _(WLR)  Equation (1)Qd _(in) =Qd _(out) −Q _(F)   Equation 1A

the control unit may receive set values for n−2 of said flow rates(Q_(INF1), Q_(INF2), Q_(F), Qd_(in), Qd_(out), Q_(WLR)), and calculatethe remaining 2 using equations 1 and 1A.

The above also applies to the configuration of FIG. 4 noting that absentany infusion then:Q _(F) =Q _(WLR)   Equation 1Qd _(in) =Qd _(out) −Q _(F)   Equation 1A

and therefore it is sufficient for the control unit to know for examplethe value of the desired weight loss rate and that of one of Qd_(in),Qd_(out) to have all settings necessary to control the apparatus fluidlines.

In accordance with aspects of the invention, the control unit 10 isfurther configured for receiving one or more values of a parameterrelated to the concentration of lactate Cd_(in) of the fresh treatmentliquid flowing in the preparation line 19: for instance control unit 10,e.g. acting on preparation section 100, may keep the concentration ofthe lactate Cd_(in) in the fresh treatment liquid constant at a setvalue Cd_(set) (e.g., imposed by the operator via user interface 12).Cd_(set) would therefore represent the value of the parameter related tothe concentration of lactate Cd_(in) of the fresh treatment liquid. Inmost treatments, the concentration of lactate in the fresh treatmentliquid is kept at a same set value Cd_(set) all along the treatment timeTt; it is however not excluded that the concentration of lactate in thefresh dialysis liquid may be changed and e.g., kept at a first constantvalue Cd_(set1) for a time interval ΔT₁ and then moved up or down to adifferent constant value Cd_(set2) for a subsequent time interval ΔT₂(see FIG. 1). For example the control unit may keep the concentration oflactate in the fresh treatment liquid constant at said set valueCd_(set) during a time interval ΔT lasting at least 10% of said totaltreatment time Tt, or at least 30% of said total treatment time Tt or atleast 70% of said total treatment time Tt, or the entire treatment totaltime Tt. In most practical cases, the control unit may be configured forkeeping the fresh treatment liquid at a concentration of lactate Cd_(in)fixed at a set value Cd_(set) comprised between 35 mmol/l and 45 mmol/l,preferably between 40 mmol/l and 45 mmol/l.

The control unit 10 is also configured for receiving one or moremeasured values of a parameter related to the concentration of lactateCd_(out) in the used treatment liquid flowing in the spent dialysateline 13 and for computing at least one value of a parameter D, KTindicative of the effectiveness of the extracorporeal blood treatment.At this purpose, the apparatus 1 may include an outlet lactateconcentration sensor 50, which may be operative at said spent dialysateline 13 and be connected to the control unit: this latter is configuredto receive, as measured value or values, of the parameter related to theconcentration of lactate Cd_(out) in the used treatment liquid, one ormore measured values of the lactate concentration Cd_(out) detected inreal time by the lactate concentration sensor. Use of a lactateconcentration sensor 50 located in the spent dialysate line 13 allows tomeasure the instantaneous value of lactate concentration and thus thecontrol unit 10 may be configured to receive said measured value(s) ofinstantaneous lactate concentration(s) and to calculate in real timeinstantaneous value(s) of the parameter D, KT indicative of theeffectiveness of the extracorporeal blood treatment. This may berepeated a plurality of times in the course of the treatment therebymonitoring in real time the value of the effectiveness parameter, stillwith no negative impact on treatment prescription as lactateconcentration may follow its prescribed value. The lactate concentrationsensor 50 may be located in the spent dialysate line itself: forinstance the lactate concentration sensor 50 may be located in a tractof the spent dialysate line upstream the branch off point 51 of theultrafiltration line 25 (see FIGS. 3 and 4) or it may be located on thespent dialysate line 13 downstream the branch off point 51 of theultrafiltration line (see FIGS. 3 and 4 where sensor is represented indashed tract on line 13). Alternatively, the sensor 50 may be located ona line branching off the spent dialysate line such as on ultrafiltrationline 25 or on any other line branching off the spent dialysate line andconfigured to receive the fluid or part of the fluid flowing in thespent dialysate line.

In case of evaluation of a whole treatment session, then it mayalternatively be envisaged to collect the spent fluid which has flown inthe spent dialysate line (or samples of said spent fluid sampled atregular intervals) and measure the concentration of lactate in thecollected fluid with an appropriate sensor. For example, in the circuitshown in FIGS. 3 and 4 the fluid collected in container 23 or incontainer 14 may be representative of the fluid that has flown in thespent dialysate line during the treatment.

In further detail and with reference to the flow chart of FIG. 5, in thecase where the efficiency parameter is monitored in real time, thecontrol unit may be configured for keeping the concentration of lactatein the fresh treatment liquid Cd_(in) constant at said set valueCd_(set) during a time interval ΔT (step 201) and for receiving one ormore measured values of a parameter related to the concentration oflactate Cd_(out) of the used treatment liquid flowing in the spentdialysate line from said sensor 50 (step 202); in particular, themeasurements of the parameter related to the concentration of lactateCd_(out) are taken during the time interval ΔT or during a further timeinterval ΔT′ having same duration of said time interval ΔT but delayedof an hydraulic delay with respect to said time interval. In otherwords, the measures of the value(s) Cd_(out) in the used treatmentliquid are related to a liquid which corresponds to the fresh treatmentliquid at the known value Cd_(set) of lactate concentration after thisfresh liquid has passed through the secondary chamber of the bloodtreatment unit and reached the lactate concentration sensor.

As mentioned, (step 203) the control unit 10 may then calculate theeffectiveness parameter D, KT: the calculation may be done a pluralityof consecutive times during said time interval ΔT in order to get areliable indication of the development of the actual effectiveness ofthe treatment. In particular, the control unit then calculates the valueof the parameter D, KT indicative of the effectiveness of theextracorporeal blood treatment based on:

the one or more measured values of the parameter related to theconcentration of lactate Cd_(out) of the used treatment liquid;

the one or more values of the parameter related to the concentration oflactate Cd_(in) of the fresh treatment liquid (in practice based onCd_(set));

the value of said flow rate Qd_(in) of fresh treatment liquid or of saidflow rate Qd_(out) of used treatment liquid.

Additionally, the control unit may receive or store a valuerepresentative of the concentration of lactate in blood Cb_(in): thisvalue may be a constant value or a value set by the physician based onknowledge of the specific patient. The applicant noted that lactateconcentration in arterial blood at the beginning of a treatment sessionis slightly less than 1 mmol/l and changes only slightly during thedialysis session: the average increase being between 2 and 4 mmol/literand taking place in the first minutes of blood treatment. This meansthat if the calculation is made using measured values taken after theinitial minutes of extracorporeal blood treatment, then considering asset value for the lactate concentration in blood e.g. 4 mmol/l does notsignificantly affect accuracy of the calculation of the effectivenessparameter. Thus, the control unit may accurately calculate the value ofthe parameter D, KT indicative of the effectiveness of theextracorporeal blood treatment based on the above indicated values andalso on the value of the concentration of lactate in blood Cb_(in),which is normally taken between 3 and 5 mmol/l.

In accordance with an aspect the parameter indicative of theeffectiveness of the extracorporeal blood treatment is lactatedialysance D, and in particular effective lactate dialysance, which iscalculated using the following formula:D=(Qdin ×(Cdin Cdout)+QF×Cdout)/(Cdin Cbin)  Equation (2)

where

D is the calculated value of dialysance for lactate,

Cd_(out) is the measured value of the parameter related to theconcentration of lactate, in particular the lactate concentration, ofthe used treatment liquid;

Cd_(in) is measured value of the parameter related to the concentrationof lactate, in particular the lactate concentration, of the freshtreatment liquid;

Qd_(in) is the flow rate of fresh treatment liquid;

Cb_(in) is the value representative of the concentration of lactate inblood or in a blood component (plasma);

Q_(F) is the value of ultrafiltration flow rate through thesemipermeable membrane.

When no ultrafiltration through the semipermeable membrane is present(Q_(F)=0), then the above formula takes the following simplified form:D=D0=(Qdin ×(Cdin Cdout))/(Cdin Cbin)  Equation (3)

Note that for the purpose of calculation of the effectiveness parameterand in particular of dialysance the control unit is configured to keepconstant both the flow rate Qd_(in) of fresh treatment liquid in thepreparation line 19 and the flow rate Qb of patient's blood in theextracorporeal blood circuit; in practice while the measure(s) ofCd_(out) is/are taken (e.g., during ΔT or ΔT′), the concentrationCd_(in) of lactate in the fresh treatment liquid and the flow rates offresh treatment liquid Qd_(in) and of blood Qb are all kept constant.

The above calculated value of D is an effective dialysance and thusaccounts for both the performances of the membrane of the bloodtreatment unit and for any recirculation at access level (i.e.recirculation of treated blood between the venous or return line and thearterial or withdrawal line of the extracorporeal blood circuit).

The control unit may also be configured to determine presence or atleast a suspect of the presence of recirculation at fistula level and/orto calculate an amount of recirculation at fistula level (step 204) bycomparing the detected dialysance value D with a reference value (whichmay be a constant reference value or a value of dialysance measured forthe same patient in previous treatments).

Once the dialysance for lactate has been calculated, the control unitmay also calculate and display (e.g., via user interface 12) thedialysance for a given solute different from lactate (step 205).

In greater detail, according to a further aspect of the invention andwith reference to FIG. 6, the control unit 10 is configured to calculatedialysance for a given substance different from lactate (e.g., ureadialysance) based on the calculated value of the dialysance for lactate.The purpose of calculating D_(solute) (or K_(solute)) for a solutedifferent from lactate may also be that of allowing to estimate thesolute dialysis dose (KT)_(solute), for example for a solute like urea.Note that while clearance and dialysance are dimensionally expressed asflow rates (e.g., mL/min), dialysis dose is usually expressed as KT/V(which is a “dimensionless ratio”) or in a non-normalized manner simplyas KT (which is a volume and can be expresses e.g., in mL or Liters),where:

K—dialyzer clearance/dialysance of urea/other solute,

T—dialysis time,

V—volume of distribution of urea/solute, approximately equal topatient's total body water.

The calculation of dialysance or clearance for the given solute (e.g.urea) comprises, for example, the following steps, which rely on use ofone parameter, namely the mass transfer coefficient, which is anexpression of the performance characteristics of a dialyzer membrane.

In particular, in the case of purely diffusive mass transfer, dialysanceor clearance may be expressed as a function of the solute mass transfercoefficient K0.A of the specific dialyzer. Mass transfer K0.A reflectssolute diffusion in the dialysis membrane and fluid compartments,dependents on solute size and decreases when solute molecular weightincreases. The term ‘K0.A’ matches with the asymptotic dialysance thedialyzer would deliver at infinite flow rates.

With the aim of calculating dialysance or clearance for the given solute(e.g. urea) different from lactate, the control unit derives first amass transfer coefficient (K0.A)_(lactate) for lactate of the membraneof the treatment unit.

For instance using the following formula, which is valid only in thecase where no ultrafiltration occurs. This means Q_(F)=0 but also thatinternal phenomenon of filtration/backfiltration is not considered bythis equation. In these conditions inlet and outlet flow rates areequal, namely Qd_(in)=Qd_(out).

$\begin{matrix}{( {K\; 0.A} )_{lactate} = {{K\; 0.A} = {{Qb} \times \frac{{Ln}( \frac{1 - {Z \times E}}{1 - E} )}{1 - Z}}}} & {{Equation}\mspace{14mu}(4)} \\{{{With}\mspace{14mu} E} = \frac{D\; 0}{Qb}} & \; \\{{{With}\mspace{14mu} Z} = {{\frac{Qb}{Qd}\mspace{14mu}{and}\mspace{14mu}{NT}} = \frac{K\; 0 \times A}{Qb}}} & \;\end{matrix}$

Note that in the above formula the value of dialysance at zeroultrafiltration is used. In case the value of dialysance (in this caselactate dialysance) at zero ultrafiltration (Q_(F)=0) is not availablethen there are at least two ways to estimate dialysance D0 at zeroultrafiltration as a function of a dialysance value D obtained atnon-zero filtration.

$\begin{matrix}{\mspace{79mu}{D = {{{{D\; 0} + \frac{QF}{2}}\;\overset{yields}{arrow}\;{D\; 0}} = {D\mspace{14mu}\frac{QF}{2}}}}} & {{Equation}\mspace{14mu}(5)} \\{\mspace{79mu}{or}} & \; \\{D = {{{{D\; 0 \times ( {1\mspace{14mu}\frac{QF}{{Qb}_{i\; n}}} )} + {QF}}\;\overset{yields}{arrow}\;{D\; 0}} = {{Qb}_{\;{i\; n}} \times \frac{D - {QF}}{{Qb}_{i\; n} - {QF}}}}} & {{Equation}\mspace{14mu}(6)}\end{matrix}$

Thus, in case a dialysance value D is available at non-zeroultrafiltration, above equations allows for estimating the dialysance atzero ultrafiltration D0 (step 301 in FIG. 6).

K0.A value (in particular (K0.A)_(lactate)) may then be derived fromthis D0 estimate using Equation 4 (step 302).

Then, based on (K0.A)_(lactate) the (K0.A) value for a different solutemay be calculated (step 303). As already mentioned mass transfercoefficient reflects solute diffusion in the dialysis membrane and fluidcompartments, it is strongly dependent on solute size and decreases whensolute molecular weight increases. Experimental data indicate that K0(or K0.A) interpolation as a function of solute molecular weight is apower law:

$\begin{matrix}{{K\; 0.A} = {{A.{mw}^{- b}} = {K\; 0.A_{ref} \times ( \frac{{mw}_{ref}}{mw} )^{b}}}} & {{Equation}\mspace{14mu}(7)}\end{matrix}$

Where ‘ref’ is a reference solute for which K0.A value is available.

Above interpolation law may be valid in a reasonably wide molecularweight range, e.g. 50 to 5000 g/mole. Urea will be often taken asreference solute, being commonly monitored and representative of thesmallest solutes (mw 60 g/mole). Power law coefficient ‘b’ may becomputed as soon as K0.A is available for two solutes of differentmolecular weight. In general coefficient ‘b’ depends upon the propertiesof the membrane 5 of the treatment unit 2: the manufacture of thetreatment unit generally provides data sheets with in vitro or in vivoclearance/dialysance values over a relevant range of molecular weightsolutes (>1000 g/mole), which may be used to compute ‘b’.

For instance the following table provides reference values of K0.A foran exemplary plausible membrane used in dialysis, and which may then beused for calculating coefficient ‘b’ and then for extrapolating lactateto urea data from equation 7.

Solute Urea Vitamin B12 Lactate mw (g/mole) 60 1335 89 K0.A (ml/min) 720200 — Power law b = 0.41 — coefficient

Once the (K0.A) for a solute different from lactate has been calculated,then dialysance for said different solute may be estimated for instanceusing the following equation (step 304 in FIG. 6):

$\begin{matrix}{D = \frac{{{Qb}_{i\; n} \times {Qd}_{i\; n}} - {f \times ( {{Qb}_{i\; n} - {QF}} ) \times ( {{Qd}_{i\; n} + {QF}} )}}{{Qd}_{i\; n} - {f \times ( {{Qb}_{i\; n} - {QF}} )}}} & {{Equation}\mspace{14mu}(8)} \\{\mspace{79mu}{With}} & \; \\{\mspace{79mu}{f = ( {\frac{{Qb}_{i\; n} - {QF}}{{Qb}_{i\; n}} \times \frac{{Qd}_{i\; n} + {QF}}{{Qd}_{i\; n}}} )^{1/\gamma}}} & \; \\{\mspace{79mu}{\gamma = {{\exp( \frac{QF}{K\; 0.A} )}\mspace{40mu} 1}}} & \;\end{matrix}$

where

Qb_(in)=value of the blood flow rate at the inlet of the treatment unit(this value is typically known as it is either set by the user orestimated with known methods e.g. by measuring the angular speed of theblood pump and the pressure regimen in the blood line),

Qd_(in)=value of the flow rate of fresh treatment liquid in thepreparation line 19,

QF=value of the ultrafiltration flow rate.

Alternatively, once the (K0.A) for a different solute has beencalculated, then dialysance may be calculated for using equation 4 (todetermine dialysance at zero ultrafiltration for said given solute) andthen one of equations 5 or 6 to determine dialysance at non-zeroultrafiltration for the given solute. Equation 8 may alternatively beused for computing (K0.A)_(lactate).

In summary, the control unit 10, by applying the above equations, isconfigured to calculate the dialysance for a given solute different fromlactate from:

the calculated value of the dialysance for lactate,

one or more of values of: the flow rate Qd_(in) of fresh treatmentliquid, the flow rate Qd_(out) of spent dialysate liquid, theultrafiltration flow rate Q_(F) through the semipermeable membrane;

the blood flow rate Qb or the plasma flow rate Qp (in particular themeasured or estimated values of these flow rates at the inlet of thetreatment unit);

one or more established relationships (e.g., known ratios) between thevalue of the mass transfer coefficient (K0.A)_(lactate) for lactate tothe value of the mass transfer coefficient (K0.A)_(solute) for the givensolute.

It should be noted that the equations reported in previous sectionimplicitly assume that blood and treatment fluid is ‘one-phase’ for thegiven solute. This ‘one phase’ model, using Qbin, provides results whichalthough quite accurate represent a first approximation compared toreality. A more accurate model may consider that:

solutes may not be evenly distributed between plasma and red blood cells(RBCs),

solutes transfer across RBC membrane may be ‘slow’.

According to one further aspect of the invention, depending upon thesolute, instead of blood flow Qb_(in), equations 6 and 8 above may useplasma flow rate Qp_(in) at the inlet of the blood treatment unit(Qp_(in)=Qb_(in)*(1-Hct)). Analogously, Qp_(in) may be used in equation4 for determining the K0.A value.

In particular, equations 4 and 6 may be used with Qp_(in) instead ofQp_(in), in order to arrive at the (K0.A)_(lactate) for lactate. Then,equation 7 may be used for the calculation of the K0.A value for anothersolute. If for instance this other solute is urea it may be reasonablyassumed that no concentration gradient is present between plasma andRBCs for urea, and thus transfer through the RBC membrane issufficiently fast with respect to the blood dwell time in the dialyzer.In such case equation 8 for the calculation of urea dialysance D may beused selecting whole blood flow rate Qb_(in). Instead, if dialysance ofcreatinine needs to be calculated, one should consider that creatininemass transfer through RBC membrane is slow with respect to the blooddwell time in the dialyzer; consequently creatinine inside RBCs is moreor less unchanged at dialyzer outlet. Thus, once K0.A is available forcreatinine (e.g. via equation 7), dialysance for creatinine may becalculated with equation 8 using Qp_(in) instead of Qb_(in).

In summary, again referring to FIG. 6, the control unit is configured tocalculate the dialysance for the given solute by:

measuring or calculating the value of dialysance for lactate at zeroultrafiltration (step 301),

deriving a mass transfer coefficient (K0.A)_(Lactate) for lactate of themembrane of the treatment unit (step 302) from:

the calculated value of the dialysance for lactate at zeroultrafiltration,

one or more of values of: the flow rate Qd_(in) of fresh treatmentliquid, the flow rate Qd_(out) of spent dialysate liquid, theultrafiltration flow rate Q_(F) through the semipermeable membrane, theblood flow rate Qb or the plasma flow rate Qp (in particular themeasured or estimated values of these flow rates at the inlet of thetreatment unit); Then the control unit derives the mass transfercoefficient (K0.A)_(solute) for a given solute different from lactate(step 303) relying on one or more established ratios between the valueof the mass transfer coefficient (K0.A)_(lactate) for lactate to thevalue of the mass transfer coefficient (K0.A)_(solute) for the givensolute. Subsequently, the control unit calculates the dialysance for thegiven solute different from lactate (step 304) based on either equation4 and one of equations 5 or 6 (which imply to first calculate dialysanceat zero ultrafiltration), or using equation 8 (which allow directcalculation of the dialysance at non zero ultrafiltration) using Qbin orQpin depending upon the transfer behavior of the selected solute.

In other words, once the mass transfer coefficient for the given solutehas been determined, dialysance may be calculated based on:

the derived mass transfer coefficient for the given solute(K0.A)_(solute); and

one or more of values of: the flow rate Qd_(in) of fresh treatmentliquid, the flow rate Qd_(out) of spent dialysate liquid, theultrafiltration flow rate Q_(F) through the semipermeable membrane,

the blood flow rate Qb or the plasma flow rate Qp (in particular themeasured or estimated values of these flow rates at the inlet of thetreatment unit).

In accordance with another aspect, the parameter indicative of theeffectiveness of the extracorporeal blood treatment based is the lactatedialysis dose (KT)_(lactate) delivered over a reference time period Tand the control unit may be configured to calculate (step 203 in FIG.5), in addition to dialysance, also the lactate dialysis dose(KT)_(lactate). If the time period is the total treatment time Tt duringwhich a patient is submitted to extracorporeal blood treatment the totallactate dialysis dose for lactate is indicated as (KTt)_(lactate).

The lactate dialysis dose (KT)_(lactate) delivered over a reference timeperiod T (or the total lactate dialysis dose for lactate (KTt)_(lactate)delivered over the whole treatment time) may be determined in variousways.

A first procedure may be applied if the flow rates (namely blood flowrate Qb, fresh treatment liquid flow rate Qd_(in), used treatment liquidflow rate Qd_(out) and, if present, ultrafiltration flow rate Q_(F))remain constant during the whole treatment time Tt or at least during areference time period T which may be a fraction of the whole treatmenttime. According to this first procedure, the control unit (10) may beconfigured to calculate lactate dialysis dose (KT)_(lactate) or(KTt)_(lactate) by:

determining the total effluent volume flown in the spent dialysate lineEV in the course of the reference time period T or Tt,

measuring the lactate concentration of said total effluent volume,

calculating KT or KTt for lactate based on the lactate concentration inblood, lactate concentration in the fresh treatment liquid and lactateconcentration in said effluent volume using the following formula(KT)_(lactate) =EV*((Cd _(in) −Cd _(out))/(Cd _(in) −Cb_(in)))  Equation (9)or(KTt)_(Lactate) =EV*((Cd _(in) −Cd _(out))/(Cd _(in) −Cb_(in)))  Equation (10)

where

EV: effluent volume during T or Tt respectively,

Cd_(out) is the lactate concentration of the used treatment liquid;

Cd_(in) is the lactate concentration of the fresh treatment liquid;

Cb_(in) is the concentration of lactate in blood or in a blood component(plasma).

In case during a total treatment time Tt the flow rates (namely bloodflow rate Qb, fresh treatment liquid flow rate Qd_(in), used treatmentliquid flow rate Qd_(out) and, if present, ultrafiltration flow rateQ_(F)) remain constant at respective values during correspondingconsecutive reference time periods Ti (each Ti being fraction of thewhole treatment time), then the total dialysis dose for lactateKTt_(lactate) may be calculated using the above process, namely equation9, for each reference time period Ti and then making the sum of each‘partial’ dialysis dose (KT)i_(lactate) calculated for each referencetime period Ti:

In other words, for each time period Ti equation 9 becomes:(KT)i _(lactate) =EVi*((Cd _(in) −Cd _(out))/(Cd _(in) −Cb _(in)))

where

EVi: effluent volume collected during each respective time interval

(Ti),

Cd_(out) is the lactate concentration of the used treatment liquidduring each respective time interval (Ti),

Cd_(in) is the lactate concentration of the fresh treatment liquidduring each respective time interval (Ti),

Cb_(in) is the concentration of lactate in blood or in a blood component(plasma) during each respective time interval (Ti).

The total dialysis dose for lactate (KTt)_(lactate) is then determinedmaking the sum of each partial dialysis dose for lactate (KT)i_(lactate)for each reference time period Ti as follows:(KTt)_(Lactate)=Σ(KT)i _(lactate)  Equation (11)

The above procedure requires that the spent dialysate line is connectedto a collection container where the entire spent dialysate volume iscollected or to a collection container connected with a sampling lineconfigured for regularly, e.g., periodically, sampling representativesamples of the spent dialysate over the whole treatment time or over thereference time period. Moreover, the concentration of lactate in theliquid present in the collection container (such as container 23 orcontainer 14) at the end of the treatment may need to be measured.

In the case where no representative sample(s) of the spent dialysateover the whole treatment (or over a reference time period of interest)is available, and/or flow rate changes have occurred one or more timesalong the treatment (or reference time period of interest), then thepresent invention provides for a second alternative procedure tocalculate the total lactate dialysis dose (KTt)_(Lactate) over treatmenttime Tt. In these conditions overall lactate (KTt)_(lactate) may beestimated by making a sum of a plurality of lactate dialysis dosecontributes (in a way similar to equation 11):(KTt)_(lactate)=Σ(KT)i _(lactate)=Σ(Di _(lactate) ·Ti)  Equation (12)

In greater detail, according to a second procedure, the control unit(10) may be configured to calculate lactate dialysis dose (KT)_(lactate)by:

determining lactate dialysance for a first time period (T1) during whichthe blood flow rate (Qb), the flow rate (Qd_(in)) of fresh treatmentliquid, and optionally ultrafiltration flow rate (Q_(F)), are keptconstant at first respective values;

calculating a lactate dose for the first time period multiplying theduration of the first time period times the lactate dialysancedetermined for the same first time period;

determining lactate dialysance for any further time period (Ti) duringwhich the blood flow rate (Qb), the flow rate (Qd_(in)) of freshtreatment liquid, and optionally ultrafiltration flow rate (Q_(F)), arekept constant at further respective values;

calculating a lactate dialysis dose for each one of said further timeperiods multiplying the duration of each further time period times therespective lactate dialysance determined for the same further timeperiod;

summing the calculated lactate doses for the first time period and foreach further time period to obtain the total lactate dose for thereference period (which may be total treatment time Tt) covering thefirst time period and any further time period using equation 12.

Finally, the invention provides for a third procedure in case where:

no representative sample(s) of the spent dialysate over the wholetreatment (or over a reference time period of interest) is available,

flow rate changes have occurred one or more times along the treatment(or reference time period of interest),

spent dialysate lactate concentration is only measured once during thetreatment (or during the reference time period of interest).

Under these circumstances and according to further aspects of theinvention, the control unit may be configured to calculate dialysancefor lactate at any given flow rate condition and consequently determinethe overall lactate dose (KT)_(lactate) or (Kit)_(lactate) from thesingle lactate measurement, via the computation of lactate K0.A. If, forinstance, we assume to have spent dialysate lactate concentrationmeasured during a first time period (together with the values of allneeded flow rates which remain constant during the first time periodnamely blood flow rate (Qb)₁, fresh treatment liquid flow rate(Qd_(in))₁ or used treatment liquid flow rate (Qd_(out))₁ and, ifpresent, ultrafiltration flow rate (Q_(F))₁, then lactate dialysance(D1)_(lactate) for said first time period may be determined using aboveequation 2. Consequently, the control unit may be configured todetermine the value of the lactate dialysance for a second time period(D2)_(lactate) (and in general for any further time period) at whichdifferent, but known, flow rate conditions exist based on:

the value of dialysance (D1)_(Lactate) for the first time period;

the values of blood flow rate (Qb)₂, fresh treatment liquid flow rate(Qd_(in))₂ or used treatment liquid flow rate (Qd_(out))₂ and, ifpresent, ultrafiltration flow rate (Q_(F))₂ at the second (or further)time period.

In practice, the control unit may be configured to calculate the valueof dialysance (D1)_(lactate) for the first time period (relying onequation 2 and using blood flow rate (Qb)₁, fresh treatment liquid flowrate (Qd_(in))₁ or used treatment liquid flow rate (Qd_(out))₁ and, ifpresent, ultrafiltration flow rate Q_(F1)); then the control unit maycalculate the mass transfer coefficient for lactate (K0.A)_(lactate)using equation 4 and one of equations 5 or 6. Then—based on the(K0.A)_(lactate) and the values of blood flow rate (Qb)₂, freshtreatment liquid flow rate (Qd_(in))₂ or used treatment liquid flow rate(Qd_(out))₂ and, if present, ultrafiltration flow rate (Q_(F))₂ at thesecond (or further) time period—the control unit is configured tocalculate dialysance for a second time period (D2)_(lactate) usingequation 4 and one of equations 5 or 6 (step represented by block 206 inFIG. 5). Note that, instead of equation 4, equation 8 may be used forthe above calculations.

Once the dialysance values for the second and any further time periodshave been calculated, each dialysance value is multiplied times therespective time period thereby calculating a lactate dialysis dose foreach one of said time periods; then by making the sum of the calculatedlactate doses for the first time period and for each further time period(see block 203 in FIG. 5), the control unit obtains the total lactatedose for the reference period (which may be total treatment time Tt)covering the first time period and any further time period (equation12):(KTt)_(actate)=Σ(K T)i _(lactate)=Σ(Di _(lactate) ·Ti)

The control unit may thus be configured to calculate the dialysis dosefor the entire treatment time with knowledge of the dialysance valueobtained with a single measure of spent dialysate lactate concentration,as long as there is knowledge of the flow rates (blood flow rateQb_(1 . . . n), fresh treatment liquid flow rate Qd_(in1 . . . n) orused treatment liquid flow rate Qd_(cut1 . . . n) and, if present,ultrafiltration flow rate Q_(F1 . . . n)) of the time periods duringwhich said flow rates apply.

Finally, in accordance with a further aspect the control unit mayconfigured to periodically calculate the value of the parameterindicative of effectiveness (e.g., either dialysance D and/or dialysisdose KT for instance using the procedures and equations presented above)or the control unit may calculate said parameter value upon receiving anorder form the user (e.g., via user interface) or the control unit mayautomatically trigger a new computation of the value of said parameter(D, KT) indicative of the effectiveness of the extracorporeal bloodtreatment every time the control unit receives an indication that therehas been a change (for instance a new setting entered by a user via userinterface) or detects a change (for instance a detection of a change ina real value) in one or more of following flow rates: blood flow rate(Qb), fresh treatment liquid flow rate (Qd_(in)), used treatment liquidflow rate (Qd_(out)) and, if present, ultrafiltration flow rate (Q_(F)).

EXAMPLES

1. Calculation of Lactate Dialysance at Constant Blood Flow Rate, FreshTreatment Liquid Flow Rate and Ultrafiltration Flow Rate

Blood flow:Qb=Qb _(in)=320 ml/min

Fresh treatment liquid flow rate:Qd=Qd _(in)=500 ml/min

Ultrafiltration flow rate:Q _(F)=15 ml/min

Lactate concentration lactate in fresh treatment liquid:Cd _(in)=40.0 mmol/L

Patient hematocrit:Hct=33%

Lactate concentration in spent treatment liquid:Cd _(out)=25.8 mmol/L

Plasma flow rate:Qp=320×(1−0.33)=214.4 ml/min

Patient plasma lactate estimate:Cb _(in)=4 mmol/L

Lactate dialysance estimate using Equation 2:D=(500×40−515×25.8)/(40−4)=186.5 ml/min

2. Calculation of Urea Dialysance at Constant Blood Flow Rate, FreshTreatment Liquid Flow Rate and Ultrafiltration Flow Rate

The same assumptions of example 1 apply.

After calculation of lactate dialysance with equation 2, then dialysanceat zero ultrafiltration may be estimated with equation 5 or 6.

Subsequently, using equation 4, the mass transfer coefficient(K0.A)_(lactate) for lactate is determined, which is(K0.A)_(Lactate)=547 ml/min.

Afterwards, using equation 7 (which requires the knowledge of the valueof the mass transfer coefficient (K0.A) for two solutes), the value ofthe mass transfer coefficient (K0.A)_(solute) for the given solute (inthis case urea) may be calculated, which is (K0.A)_(solute)=647 ml/min.

Finally, using equation 8, it is possible to determine urea dialysanceD_(u)r_(ea)=239.5 ml/min

3. Calculation of Dialysance and of Dialysis Dose Based on Knowledge ofDialysance at First Values of Blood Flow Rate, Fresh Treatment LiquidFlow Rate and Ultrafiltration Flow Rate

This example shows:

calculation of dialysance at first flow rate conditions defined by knownvalues blood flow rate Qb₁, fresh treatment liquid flow rate Qd_(in1) orused treatment liquid flow rate Qd_(out1) and ultrafiltration flow rateQ_(F1) which are stable for a first time period; the calculation is maderelying on equation 1 and using a measured value of Cd_(out1) takenduring the first time period;

calculation of dialysance at second flow rate conditions of blood flowrate Qb₂, fresh treatment liquid flow rate Qd_(in2) or used treatmentliquid flow rate Qd_(out2) and ultrafiltration flow rate Q_(F2), whichare stable for a second time period consecutive to the first timeperiod;

calculation of KT for the first and second time periods;

calculation of total treatment time KT.

First Time Period Conditions

Blood flow:Qb=Qb _(in)=320 ml/min

Fresh treatment liquid flow rate:Qd=Qd _(in)=500 ml/min

Ultrafiltration flow rate:Q _(F)=15 ml/min

Concentration of lactate in fresh treatment liquid:Cd _(in)=40.0 mmol/L

Patient hematocrit:Hct=33%

Lactate concentration in spent treatment liquid:Cd _(out)=25.8 mmol/L

Plasma flow rate:Qp=320×(1−0.33)=214.4 ml/min

Patient plasma lactate estimate:Cb _(in)=4 mmol/L

Second Time Period Conditions (Change of Blood Flow Rate)

Blood flow:Qb=Qb _(in)=260 ml/min

Fresh treatment liquid flow rate:Qd=Qd _(in)=500 ml/min

Ultrafiltration flow rate:Q _(F)=15 ml/min

Concentration of lactate in fresh treatment liquid:Cd _(in)=40.0 mmol/L

Patient hematocrit:Hct=33%

Lactate concentration in spent treatment liquid:Cd _(out)=not knownPlasma flow rate:Qp=260×(1−0.33)=174.2 ml/min

Patient plasma lactate estimate:Cb _(in)=4 mmol/L

Overall Period Time Period 1 Time Period 2 treatment Time 2 h 30 1 h 304 h 00 Qd, Q_(F), Hct, Same as §3.2 Cd_(in) Qb 320 ml/min 260 ml/min Qp214 ml/min 174 ml/min D_(lactate) 184.4 ml/min 161.1 ml/minK0.A_(lactate) 565 ml/min 547 ml/min 547 ml/min K.T_(lactate) 59.7 L41.9 L 101.6 L

Control unit

As already indicated the apparatus according to the invention makes useof at least one control unit. This control unit may comprise a digitalprocessor (CPU) with memory (or memories), an analogical type circuit,or a combination of one or more digital processing units with one ormore analogical processing circuits. In the present description and inthe claims it is indicated that the control unit is “configured” or“programmed” to execute certain steps: this may be achieved in practiceby any means which allow configuring or programming the control unit.For instance, in case of a control unit comprising one or more CPUs, oneor more programs are stored in an appropriate memory: the program orprograms containing instructions which, when executed by the controlunit, cause the control unit to execute the steps described and/orclaimed in connection with the control unit. Alternatively, if thecontrol unit is of an analogical type, then the circuitry of the controlunit is designed to include circuitry configured, in use, to processelectric signals such as to execute the control unit steps hereindisclosed.

While the invention has been described in connection with what ispresently considered to be the most practical and preferred embodiments,it is to be understood that the invention is not to be limited to thedisclosed embodiments, but on the contrary, is intended to cover variousmodifications and equivalent arrangements included within the spirit andthe scope of the appended claims.

The invention claimed is:
 1. An apparatus for extracorporeal treatmentof blood comprising: a preparation line having one end configured forbeing connected to an inlet of a secondary chamber of a treatment unit,a semi-permeable membrane separating said secondary chamber from aprimary chamber of the same treatment unit; a spent dialysate linehaving one end configured for being connected to an outlet of saidsecondary chamber; and a control unit configured for commandingexecution of the following steps: causing a fresh treatment liquid toflow in the preparation line towards the secondary chamber at a flowrate, the treatment liquid including lactate; causing a used treatmentliquid to flow in the spent dialysate line at a flow rate; receiving oneor more measured values of a parameter related to the concentration oflactate in the used treatment liquid flowing in the spent dialysateline; and computing at least one value of a parameter indicative of theeffectiveness of the extracorporeal blood treatment based on: said oneor more measured values of the parameter related to the concentration oflactate of the used treatment liquid; and at least one of: said flowrate of fresh treatment liquid and said flow rate of used treatmentliquid.
 2. The apparatus according to claim 1, wherein the control unitis further configured for receiving one or more values of a parameterrelated to the concentration of lactate of the fresh treatment liquidflowing in the preparation line.
 3. The apparatus according to claim 2,wherein the step of receiving one or more values of a parameter relatedto the concentration of lactate of the fresh treatment liquid flowing inthe preparation line includes one of: measuring one or more actualvalues of the parameter related to the concentration of lactate of thefresh treatment liquid flowing in the preparation line, retrieving froma memory one or more preset values of the parameter related to theconcentration of lactate of the fresh treatment liquid flowing in thepreparation line, or receiving from a user interface one or more inputvalues of the parameter related to the concentration of lactate of thefresh treatment liquid flowing in the preparation line.
 4. The apparatusaccording to claim 2, wherein computing at least one value of aparameter indicative of the effectiveness of the extracorporeal bloodtreatment is based on: said one or more measured values of the parameterrelated to the concentration of lactate of the used treatment liquid;said one or more values of the parameter related to the concentration oflactate of the fresh treatment liquid; and at least one of: said flowrate of fresh treatment liquid or said flow rate of used treatmentliquid.
 5. The apparatus according to claim 4, wherein the step ofcausing a fresh treatment liquid to flow in the preparation linecomprises the sub-step of maintaining, at least for a time interval, theconcentration of the lactate in the fresh treatment liquid constant at aset value which represents the value of the parameter related to theconcentration of lactate of the fresh treatment liquid used forcomputing the at least one value of a parameter indicative of theeffectiveness of the extracorporeal blood treatment.
 6. The apparatusaccording to claim 5, wherein said one or more measured values of theparameter related to the concentration of lactate in the used treatmentliquid are representative of measures of the parameter related to theconcentration of lactate taken during one of: said time interval, or afurther time interval delayed by a hydraulic delay with respect to saidtime interval.
 7. The apparatus according to claim 1, wherein thecontrol unit is further configured for: receiving a total treatmenttime, which is a time during which the apparatus operates with blood inthe extracorporeal circuit and a patient connected to the extracorporealcircuit; maintaining the concentration of the lactate in the freshtreatment liquid constant at said set value during a time intervallasting for a significant portion of the treatment time; and calculatinga plurality of consecutive times during said time interval the value ofthe parameter indicative of the effectiveness of the extracorporealblood treatment, wherein said significant portion of the treatment timecomprising a portion of time is selected from the group consisting of:at least 10% of said total treatment time (Tt), at least 30% of saidtotal treatment time (Tt), at least 70% of said total treatment time(Tt), and the entire treatment total time (Tt).
 8. The apparatusaccording to claim 1, further comprising: an outlet lactateconcentration sensor connected to the control unit, the outlet lactateconcentration sensor being operative at one of: said spent dialysateline, a line connected to the spent dialysate line, or a line connectedto the outlet of said secondary chamber, wherein the outlet lactateconcentration sensor is configured for measuring one or more real valuesof the lactate concentration lactate in the fluid exiting from thesecondary chamber, and wherein the control unit is configured toreceive, a measured value or values of the parameter related to theconcentration of lactate in the used treatment liquid, the one or moremeasured real values of the lactate concentration detected by the outletlactate concentration sensor.
 9. The apparatus according to claim 1,wherein the apparatus includes at least a blood pump configured tooperate on an extracorporeal blood circuit connectable to the primarychamber of said blood treatment unit, said control unit being connectedto the blood pump and being configured to: operate the blood pump tocause flow of a patient's blood in the extracorporeal blood circuit at ablood flow rate, receive or store a value representative of theconcentration of lactate in the patient's blood or in a blood componentof the patient's blood, and wherein the parameter indicative of theeffectiveness of the extracorporeal blood treatment is calculated basedon: at least one measured value of the parameter related to theconcentration of lactate in the used treatment liquid; at least onemeasured value of the parameter related to the concentration of lactatein the fresh treatment liquid; said flow rate of fresh treatment liquid;and said value representative of the concentration of lactate in thepatient's blood or in the blood component of the patient's blood. 10.The apparatus according to claim 6, wherein, at least during said timeinterval or during said further time interval, the control unit isconfigured to keep constant the flow rate of fresh treatment liquid inthe preparation line, the flow rate of the patient's blood in theextracorporeal blood circuit, and the flow rate of ultrafiltration flowthrough the semipermeable membrane.
 11. The apparatus according to claim1, wherein the parameter indicative of the effectiveness of theextracorporeal blood treatment is lactate dialysance, which iscalculated using the following formula:D=(Qdin×(Cdin−Cdout)+QP×Cdout)/(Cdin−Cbin) where D is the calculatedvalue of dialysance for lactate, Cd_(out) is the measured value of theparameter related to the concentration of lactate of the used treatmentliquid, Cd_(in) is measured value of the parameter related to theconcentration of lactate of the fresh treatment liquid, Qd_(in) is theflow rate of fresh treatment liquid; Cb_(in) is the value representativeof the concentration of lactate in blood or in a blood component, andQ_(F) is the value of ultrafiltration flow rate through thesemipermeable membrane.
 12. The apparatus according to claim 1, whereinthe control unit is configured for causing the fresh treatment liquid toflow in the preparation line towards the secondary chamber at a constantlactate concentration, which is set at a set value comprised between 35mmol/l and 45 mmol/l.
 13. The apparatus according to claim 9, whereinthe value representative of the concentration of lactate in blood or ina blood component is a known value selected in the range comprisedbetween 1 and 5 mmol/l.
 14. The apparatus according to claim 1, whereinthe parameter indicative of the effectiveness of the extracorporealblood treatment is lactate dialysance, and wherein the control unit isconfigured to calculate the dialysance for a given solute different fromlactate using: the calculated value of the lactate dialysance, and oneor more established relationships between the value of a mass transfercoefficient for lactate to the value of a mass transfer coefficient forthe given solute, the mass transfer coefficient reflecting a solutediffusion through the membrane.
 15. The apparatus according to claim 14,wherein the parameter indicative of the effectiveness of theextracorporeal blood treatment is lactate dialysance, and wherein thecontrol unit is configured to calculate dialysance for a given solutedifferent from lactate, the calculation of dialysance for the givensolute comprising: deriving a mass transfer coefficient for lactate ofthe membrane of the treatment unit from the calculated value of thedialysance for lactate; determining a mass transfer coefficient of themembrane of the treatment unit for the given solute based on the valueof the mass transfer coefficient for lactate; calculating the dialysancefor the given solute based on the mass transfer coefficient for thegiven solute; and wherein the lactate dialysance and the dialysance forthe given solute different from lactate are calculated at same valuesof: the flow rate of fresh treatment liquid, the ultrafiltration flowrate through the semipermeable membrane, and the blood flow rate in theextracorporeal circuit.
 16. The apparatus according to claim 14, whereinthe control unit is further configured for: identifying the solute forwhich dialysance is to be calculated; determining if a mass transfertime of the solute through red blood cells is greater, optionally atleast 5 times greater, than a blood dwell time of blood flowing throughthe blood treatment unit; and using the value of the plasma flow rate atthe inlet of the blood treatment unit as an effective value of the bloodflow rate for the purpose of calculating the solute mass transfercoefficient, if it has been determined that the mass transfer time ofthe solute through red blood cells is greater, optionally 5 timesgreater, than a blood dwell time in the blood treatment unit, whereQp_(in)=(1−Hct)*Qb_(in), and with Qp_(in) being the plasma flow rate atthe inlet of the blood treatment unit, Hct being the hematocrit of thepatient's blood in the arterial line at the inlet of the blood treatmentunit, and Qb_(in), being the blood flow rate at the inlet of the bloodtreatment unit.
 17. The apparatus according to claim 14, wherein themass transfer coefficient for lactate of the membrane of the treatmentunit is derived by: measuring or calculating the value of dialysance forlactate, in particular at zero ultrafiltration; deriving a mass transfercoefficient for lactate of the membrane of the treatment unit from: thecalculated value of the dialysance for lactate, in particular at zeroultrafiltration, one or more of values of: the flow rate of freshtreatment liquid, the flow rate of spent dialysate liquid, theultrafiltration flow rate through the semipermeable membrane, and theblood flow rate or the plasma flow rate, in particular one of the plasmaflow rate at the inlet of the blood treatment unit and the blood flowrate at the inlet of the blood treatment unit; wherein the mass transfercoefficient for the given solute is derived using one or moreestablished relationships between the value of the mass transfercoefficient for lactate to the value of the mass transfer coefficientfor the given solute; and wherein the dialysance of the given solute iscalculated based on: one or more values of: the flow rate of freshtreatment liquid, the flow rate of spent dialysate liquid, theultrafiltration flow rate through the semipermeable membrane, one of theblood flow rate or the plasma flow rate, in particular one of the plasmaflow rate at the inlet of the blood treatment unit and the blood flowrate at the inlet of the blood treatment unit, and the determined masstransfer coefficient for the given solute.
 18. The apparatus accordingto claim 17, wherein the step of deriving a mass transfer coefficientfor lactate of the membrane of the treatment unit comprises: measuringor calculating the value of dialysance for lactate at zeroultrafiltration, and calculating the mass transfer coefficient forlactate of the membrane of the treatment unit using the calculated valueof the dialysance for lactate at zero ultrafiltration, wherein the stepof calculating dialysance of the given solute comprises: firstdetermining the value of the dialysance for the given solute, at zeroultrafiltration, based upon: the determined mass transfer coefficientfor the given solute; and one of: the flow rate of fresh treatmentliquid and the flow rate of spent dialysate liquid; or one or the bloodflow rate or the plasma flow rate, in particular one of the plasma flowrate at the inlet of the blood treatment unit and the blood flow rate atthe inlet of the blood treatment unit; and second determining dialysancefor the given solute at non-zero ultrafiltration based upon: thedetermined value of the dialysance for the given solute at zeroultrafiltration, and the value of the ultrafiltration flow rate; or thedetermined value of the dialysance for the given solute at zeroultrafiltration, the value of the ultrafiltration flow rate through thesemipermeable membrane, and one of the blood flow rate or plasma flowrate, in particular one of the plasma flow rate at the inlet of theblood treatment unit and the blood flow rate at the inlet of the bloodtreatment unit.
 19. The apparatus according to claim 1, wherein theparameter indicative of the effectiveness of the extracorporeal bloodtreatment comprises a lactate dialysis dose delivered over a referencetime period and wherein the control unit is configured to calculate thelactate dialysis dose by: determining the total effluent volume flowthrough the spent dialysate line in the course of the reference timeperiod, and measuring the lactate concentration of said total effluentvolume, or wherein the control unit is configured to calculate lactatedialysis dose by: receiving said one or more values of a parameterrelated to the concentration of lactate of the fresh treatment liquidflowing in the preparation line measured during the reference timeperiod, receiving values of the following flow rates, which remainconstant during the time period: blood flow rate, one of fresh treatmentliquid flow rate or used treatment liquid flow rate, and, if present,ultrafiltration flow rate, calculating a value of lactate dialysance forsaid time period, and calculating a lactate dialysis dose for said timeperiod multiplying the duration of the time period times the lactatedialysance-determined for the same time period.
 20. The apparatusaccording to claim 1, wherein the control unit is configured toautomatically trigger a new computation of at least one value of saidparameter indicative of the effectiveness of the extracorporeal bloodtreatment every time the control unit receives an indication that therehas been a change or detects a change in one or more of: blood flowrate, fresh treatment liquid flow rate, used treatment liquid flow rate,and, if present, ultrafiltration flow rate.